Tick to table: a scoping review on the global impact of alpha-gal syndrome

Alpha-gal syndrome (AGS) is a tick-associated, IgE-mediated allergy to galactose-α-1,3-galactose (alpha-gal), an oligosaccharide found on non-primate mammalian cells expressed by various bacteria and parasites, including ticks. First identified in 2009, cases are primarily associated with tick bites, which can sensitize the human immune system to alpha-gal. Subsequent exposure to alpha-gal, typically through red meat consumption, can cause severe allergic reactions, including hives, angioedema, gastrointestinal distress, and life-threatening anaphylaxis. Alpha-gal syndrome is a global phenomenon, with cases reported on six continents. In North America, AGS is most prevalent in the Southern, Central, and Eastern regions of the USA with regional pockets of higher prevalence. The number of reported cases has steadily increased owing to improved awareness, diagnostics, and the expanding range of Amblyomma americanum (L., 1758), the primary tick associated with the incidence of AGS. Alpha-gal syndrome remains underdiagnosed because of low provider and public awareness, cross-disciplinary disconnects, and the atypical clinical presentation. Although the link between tick bites and AGS is well established, critical questions remain. Why do ticks trigger this reaction among the many organisms that express alpha-gal? What has caused the rapid increase in cases and why do only some individuals develop an allergic immune response? This scoping review explores the history of alpha-gal and AGS, the role of multiple tick species and other parasites, AGS etiology and pathogenesis, and the ecological-epidemiological landscape of this emerging tick-associated allergy.